Broadscale phage therapy is unlikely to select for widespread evolution of bacterial resistance to virus infection.

Multi-drug resistant bacterial pathogens are alarmingly on the rise, signaling that the golden age of antibiotics may be over. Phage therapy is a classic approach that often employs strictly lytic bacteriophages (bacteria-specific viruses that kill cells) to combat infections. Recent success in using phages in patient treatment stimulates greater interest in phage therapy among Western physicians. But there is concern that widespread use of phage therapy would eventually lead to global spread of phage-resistant bacteria and widespread failure of the approach. Here, we argue that various mechanisms of horizontal genetic transfer (HGT) have largely contributed to broad acquisition of antibiotic resistance in bacterial populations and species, whereas similar evolution of broad resistance to therapeutic phages is unlikely. The tendency for phages to infect only particular bacterial genotypes limits their broad use in therapy, in turn reducing the likelihood that bacteria could acquire beneficial resistance genes from distant relatives via HGT. We additionally consider whether HGT of clustered regularly interspaced short palindromic repeats (CRISPR) immunity would thwart generalized use of phages in therapy, and argue that phage-specific CRISPR spacer regions from one taxon are unlikely to provide adaptive value if horizontally-transferred to other taxa. For these reasons, we conclude that broadscale phage therapy efforts are unlikely to produce widespread selection for evolution of bacterial resistance.

Single stream inertial focusing in a straight microchannel.

In the past two decades, microfluidics has become of great value in precisely aligning cells or microparticles within fluids. Microfluidic techniques use either external forces or sheath flow to focus particulate samples, and face the challenges of complex instrumentation design and limited throughput. The burgeoning field of inertial microfluidics brings single-position focusing functionality at throughput orders of magnitude higher than previously available. However, most inertial microfluidic focusers rely on cross-sectional flow-induced drag force to achieve single-position focusing, which inevitably complicates the device design and operation. In this work, we present an inertial microfluidic focuser that uses inertial lift force as the only driving force to focus microparticles into a single position. We demonstrate single-position focusing of different sized microbeads and cells with 95-100% efficiency, without the need for secondary flow, sheath flow or external forces. We further integrate this device with a laser counting system to form a sheathless flow cytometer, and demonstrated counting of microbeads with 2200 beads s(-1) throughput and 7% coefficient of variation. Cells can be completely recovered and remain viable after passing our integrated cytometry system. Our approach offers a number of benefits, including simplicity in fundamental principle and geometry, convenience in design, modification and integration, flexibility in focusing of different samples, high compatibility with real-world cellular samples as well as high-precision and high-throughput single-position focusing.